We will study the induction of metastases from embryonal carcinoma cells (ECC) conditioned by embryonic culture systems. Preliminary studies have shown that 402AX is normally a nonmetastatic embryonal carcinoma that, if placed in contact with trophoblasts or mouse embryonic fibroblasts, becomes metastatic. Using the above experimental design, a comparative analysis of nascent soluble factors, cell contact requirements, host factors and chemicals known to modify differentiation will be pursued. A series of experiments is designed to determine the necessary biological conditions surrounding this model system. These experiments will involve physical separation, alteration and irradiation of trophoblasts and mouse embryonic fibroblasts in order to determine if their effects are maintained. The final experiment will examine the biochemical aspects of this model system to determine what alterations are conferred on ECC that enable them to become metastatic. The overall objective of this research is to determine: (1)\why ECC, when co-cultivated with trophoblasts or mouse embryonic fibroblasts, become metastatic; (2)\why trophoblasts are greater than mouse embryonic fibroblasts in producing this response; (3)\what are the biochemical and cellular changes that accompany the metastatic phenotype; and (4)\if this model parallels the normal cell movements that occur during morphogenesis, since we are dealing with an embryonic tumor, that, when placed in an embryonic environment, metastasizes.